Abstract
In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and 152 healthy matched controls using polymerase chain reaction-restriction fragment length polymorphism analysis. In functional assay, quantitative real-time polymerase chain reaction was performed to assess constitutive IRF3 mRNA expression in peripheral blood mononuclear cells from healthy subjects with different IRF3 promoter haplotypes. Among eight SNPs genotyped, an IRF3 SNP at -925 was found to be associated with SLE after correction for multiple tests (corrected P = 0.016). Of total five IKF3 SNPs genotyped, the promoter IRF3 SNPs -925A/G and -776C/T showed the most significant association with SLE. With regard to -925A/G, the frequency of GG genotype was significantly decreased among SLE patients compared with the control group (1.5% vs. 9.9%; χ2=10.0, P = 0.0015, odds ratio 0.12, 95% confidence interval 0.027-0.554). Our experimental data indicated that constitutive IRF3 mRNA expression was significantly lower in cells carrying the minor G-T/G-T haplotype pair compared with those carrying the major A-C haplotype. In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE.
| Original language | English |
|---|---|
| Pages (from-to) | 568-574 |
| Number of pages | 7 |
| Journal | Lupus |
| Volume | 17 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jul 15 2008 |
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All Science Journal Classification (ASJC) codes
- Rheumatology
Cite this
Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus. / Akahoshi, M.; Nakashima, H.; Sadanaga, A.; Miyake, K.; Obara, K.; Tamari, M.; Hirota, T.; Matsuda, A.; Shirakawa, T.
In: Lupus, Vol. 17, No. 6, 15.07.2008, p. 568-574.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus
AU - Akahoshi, M.
AU - Nakashima, H.
AU - Sadanaga, A.
AU - Miyake, K.
AU - Obara, K.
AU - Tamari, M.
AU - Hirota, T.
AU - Matsuda, A.
AU - Shirakawa, T.
PY - 2008/7/15
Y1 - 2008/7/15
N2 - In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and 152 healthy matched controls using polymerase chain reaction-restriction fragment length polymorphism analysis. In functional assay, quantitative real-time polymerase chain reaction was performed to assess constitutive IRF3 mRNA expression in peripheral blood mononuclear cells from healthy subjects with different IRF3 promoter haplotypes. Among eight SNPs genotyped, an IRF3 SNP at -925 was found to be associated with SLE after correction for multiple tests (corrected P = 0.016). Of total five IKF3 SNPs genotyped, the promoter IRF3 SNPs -925A/G and -776C/T showed the most significant association with SLE. With regard to -925A/G, the frequency of GG genotype was significantly decreased among SLE patients compared with the control group (1.5% vs. 9.9%; χ2=10.0, P = 0.0015, odds ratio 0.12, 95% confidence interval 0.027-0.554). Our experimental data indicated that constitutive IRF3 mRNA expression was significantly lower in cells carrying the minor G-T/G-T haplotype pair compared with those carrying the major A-C haplotype. In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE.
AB - In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and 152 healthy matched controls using polymerase chain reaction-restriction fragment length polymorphism analysis. In functional assay, quantitative real-time polymerase chain reaction was performed to assess constitutive IRF3 mRNA expression in peripheral blood mononuclear cells from healthy subjects with different IRF3 promoter haplotypes. Among eight SNPs genotyped, an IRF3 SNP at -925 was found to be associated with SLE after correction for multiple tests (corrected P = 0.016). Of total five IKF3 SNPs genotyped, the promoter IRF3 SNPs -925A/G and -776C/T showed the most significant association with SLE. With regard to -925A/G, the frequency of GG genotype was significantly decreased among SLE patients compared with the control group (1.5% vs. 9.9%; χ2=10.0, P = 0.0015, odds ratio 0.12, 95% confidence interval 0.027-0.554). Our experimental data indicated that constitutive IRF3 mRNA expression was significantly lower in cells carrying the minor G-T/G-T haplotype pair compared with those carrying the major A-C haplotype. In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE.
UR - http://www.scopus.com/inward/record.url?scp=46849113681&partnerID=8YFLogxK
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U2 - 10.1177/0961203308089340
DO - 10.1177/0961203308089340
M3 - Article
C2 - 18539711
AN - SCOPUS:46849113681
VL - 17
SP - 568
EP - 574
JO - Lupus
JF - Lupus
SN - 0961-2033
IS - 6
ER -